1,8-Diazabicyclo(5.4.0)undec-7-ene → ethyl 6-(N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}carbamoyl)hexanoate

HRID 9970Notes

Reaction equation

HRID 9970 reaction equation
N12CCCN=C1CCCCC2.[NH2:12][CH2:13][C:14]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:15]=1[C:16](=[O:32])[N:17]([CH:24]1[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31])[C:18]2=[O:23].[CH2:33]([O:35][C:36](=[O:45])[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][C:42](Cl)=[O:43])[CH3:34]>CC#N>[O:31]=[C:25]1[CH:24]([N:17]2[C:16](=[O:32])[C:15]3[C:19](=[CH:20][CH:21]=[CH:22][C:14]=3[CH2:13][NH:12][C:42]([CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][C:36]([O:35][CH2:33][CH3:34])=[O:45])=[O:43])[C:18]2=[O:23])[CH2:29][CH2:28][C:27](=[O:30])[NH:26]1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 543232Ethyl 6-(Chloroformyl)hexanoateHCID 219885264-(Aminomethyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

Product 1

HCID 10226304ethyl 6-(N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}carbamoyl)hexanoateYield 50%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.65 g, 4.26 mmol) was added to a stirred suspension of 4-(aminomethyl)-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione hydrocbloride (0.6 g, 1.85 mmol) in CH3CN (50 ml). After stirring for 20 min, 6-(chloroformyl)hexanoic acid ethyl ester (0.46 g, 2.22 mmol) was added. The mixture was stirred at room temperature for 17 hours. The solvent was removed in vacuo and the residue was dissolved in CH2Cl2 (70 ml). The CH2Cl2 solution was washed with 1N HCl (30 ml), H2O (30 ml), brine (30 ml) and dried (MgSO4). The solvent was removed in vacuo and the residue was purified by chromatography (SiO2, CH2Cl2:EtOAc 1:1) to give ethyl 6-(N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}carbamoyl)hexanoate (0.43 g, 50%) as a white solid: mp 82–84° C.; 1H NMR (DMSO-d6) δ d 11.11 (s, 1H), 8.41 (t, J=5.6 Hz, 1H), 7.86–7.65 (m, 3H), 5.18–5.11 (dd, J=5.4 and 12.4 Hz, 1H), 4.72 (d, J=5.7 Hz, 2H), 4.05 (q, J=7.1 Ha, 2H), 2.97–2.83 (m, 1H), 2.64–2.48 (m, 2H), 2.30–2.15 (m, 4H), 2.08–2.04 (m, 1H), 1.56–1.47 (m, 4H), 1.32–1.23 (m, 2H), 1.17 (t, J=7.1 Hz, 3H), 13C NMR (DMSO-d6) δ d 172.80, 172.71, 172.52, 169.77, 167.45, 166.92, 139.49, 134.67, 133.13, 131.49, 127.04, 121.78, 59.60, 48.84, 37.57, 35.02, 33.38, 30.91, 28.08, 24.83, 24.16, 21.96, 14.09; Anal. Calcd. For C23H27N3O7: C, 60.39; H, 5.95; N, 9.18. Found: C, 60.10; H, 5.82; N, 8.82.

Workup

  1. stirringThe mixture was stirred at room temperature for 17 hours
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in CH2Cl2 (70 ml)
  4. washThe CH2Cl2 solution was washed with 1N HCl (30 ml), H2O (30 ml), brine (30 ml)
  5. dry with materialdried (MgSO4)
  6. customThe solvent was removed in vacuo
  7. customthe residue was purified by chromatography (SiO2, CH2Cl2:EtOAc 1:1)

Sources & evidence

ORD record
ord-fdcfbfbdd1714689a16e5d665ea37a08
Source dataset
uspto-grants-2006_08
Patent number
US07091353B2

Reaction notes

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